Disinfectant compositions useful against protozoan oocysts

ABSTRACT

Compounds of the formula I   IN WHICH R1 stands for hydrogen or methyl, R2, R3, R4, R5 and R6 which may be identical or different, each stands for hydrogen or alkyl radicals of 1 to 4 carbon atoms, R7 stands for an alkyl or alkenyl radical of 8 to 18 carbon atoms, n is an integer of 2 or 3 and m is zero or an integer from 1 to 4, having an excellent action against pathogenic bacteria and protozoans especially against oocyst of coccidia when they are used in mixture with one or several chlorinated hydrocarbons.

United States Patent Raether et al.

[ Nov. 25, 1975 DISINFECTANT COMPOSITIONS USEFUL AGAINST PROTOZOAN OOCYSTS Inventors: Wolfgang Raether, Dreieichenhain;

Helmut Diery, Kelkheim, Taunus;

Ulrich Cuntze, Hofheim, Taunus, all of Germany Hoechst Aktiengesellschaft, Frankfurt am Main, Germany Filed: Apr. 11, 1974 Appl. No.: 460,132

Assignee:

Foreign Application Priority Data Apr. 14, 1973 Germany 2319045 US. Cl. 424/211; 260/944; 260/945; 424/350; 424/351; 424/353 Int Cl. A01N 9/36 Field of Search 424/211, 350, 351, 353; 260/944, 945, 924

References Cited UNITED STATES PATENTS 11/1969 Cyba 260/945 3,591,682 7/1971 Thiolliere et al. 424/211 Primary Examiner-Leonard Schenkman Attorney, Agent, or FirmCurtis, Morris & Safford [57] ABSTRACT Compounds of the formula I in which R stands-for hydrogen or methyl, R R R, R and R which may be identical or different, each stands for hydrogen or alkyl radicals of 1 to 4 carbon atoms, R" stands for an alkyl or alkenyl radical of 8 to 9 Claims, No Drawings DISINFECTANT COMPOSITIONS USEFUL AGAINST PROTOZOAN OOCYSTS I This invention relates to a disinfectant.

lt especially relates to a disinfectant effective against pathogenic bacteria and protozoans, especially against the infective stages, i.e., the oocysts of different species of coccidia which is especially used for the disinfection of stables and outruns.

Coccidia, the microorganism causing coccidiosis, are protozoans which are to be found in all species of fowls, in birds and in a great number of domestic and commercially reared animals, especially rabbits, sheep, cattle, dogs and cats.

Oocysts and spores of bacteria having solid protective walls generally are hard to kill by disinfective substances because the usual disinfectants cannot penetrate into the interior of these permanent forms. This is especially true in the case of oocysts of coccidia which are especially well protected against all the usual disinfective substances by their lipoid-containing keratin walls.

A great number of substances killing oocysts are known, for example carbon disulfide, cresol, lysol, chloroform, methylene chloride, but practically all these substances need too long periods of time and too high concentrations until the effective destruction of the oocysts is reached.

A certain exception as to the period of action is carbon disulfide, however, the required concentration to be applied raises considerable drawbacks, for example, the toxicity for mammals, the combustibility of the disinfectants which involves the danger of inflammation and of the formation of explosive mixtures as well as a difficult processing in industry.

Therefore, it is the object of the invention to develop disinfective substances having a rapid and optimal disinfective action while being non toxic and not dangerous in its application.

Now it was found that compounds of the formula I in which R stands for hydrogen or methyl, R R R*, R and R which may be identical or different, each stands for hydrogen or alkyl radicals of l to 4 carbon atoms, R stands for an alkyl or alkenyl radical of 8 to 18 carbon atoms, 11 is an integer of 2 or 3 and m is zero or an integer from 1 to 4, have an excellent action against the pathogenic bacteria and protozoans mentioned above when they are used in mixture with one or several chlorinated hydrocarbons.

The compounds of the formula I are used in mixture with chlorinated organic solvents, for example, methylene chloride, chloroform, carbon tetrachloride, chlorobenzene, dichlorobenzene, trichlorobenzene, tetrachlorobenzene, ethylene chloride, trichloroethane, tetrachloroethane or tetrachloroethylene. An emulsifier may, optionally, be added, for example, a fat acid polyglycol ester, an alkylbenzene sulfonate, a chlorinated paraffin sulfonate, a sulfosuccinic acid ester, an oxethylated alkyl phenol or a mixture of these compounds.

2 The compounds show a high killing effect against 00- cysts after a short time .of action.

The compounds are prepared by reacting the cyclic phosphates of the formula ll with amines of the formula III in which R, R R R R R and R as well as n and In each is defined as in formula I. The reactive components are advantageously reacted in the ratio of about 1 mol of amine to 1 mol of phosphite. ln some cases it may be suitable to use one component, preferably the amine, in a slight excess. The reaction is advantageously effected at a temperature ranging from l50C. Depending on the boiling and melting temperature of the amine used the reaction can be effected in the melt or using a suitable polar solvent, for example, water or an alcohol. The reaction products directly precipitate in pure state so that in general a special purification can be dispensed with.

When the reaction has been effected in the presence of solvents, it is only necessary to distill them off.

EXAMPLE OF PREPARATION were obtained.

R the alkyl radical having a chain distribution analogous to that of the coconut acid.

calculated:

Molecular weight: 424 found: 436

Nitrogen: calculated: 6.6 71 found: 6.4 71

The following compounds were prepared in an analogous manner:

2. 3-coconutalkyl ammonium-2.2-dimethyl-propyl-phosphorous acid R the alkyl radical having a chain distribution anal- 6.

ogous to that of the coconut acid. 3-isononylammonium-2.2-dimethyl-propyl-phosphorous acid ester Molecular weight: calculated: 365

H CH found: 380 l Nitrogen: calculated: 3.8 7! ,H N C|-| -C CH OP-H found: 3.8 7: i

7. 3-(dodecyl-dimethyl-amm0nium)-2.2-dimethyl-pro- 3. pyl-phosphorous acid ester 3-[ 2-( 2-dodecyla'minoethyl )-aminoethyl-amm0nium]- l5 2.2.dimethyl-propyl-phosphorous acid ester 3 3 3 a c.2 s C 2 C 2 H CH, o l 8- 1 l u C,2H2,,NH-(CH2)2NH(CH2)2NCH2CCH2OTH H CH 0* Molecular weight: Calc l t d; 431 3-(dodecyl-diethyl-ammonium)-l-methyl-propyl-phosfound: 440 phorous acid ester Nitrogen: Calculated: 10.0 74

found: 9.7 '7:

CH H") z 5 ll C H ,,lTCH CH -ClH-OT-H C H,, CH 0" 4. 3-( coconutalkylaminopropylammonium )-propyl-phos- 9 phorous ester 3-(decyl-butyl-ammonium)-2.Z-diethyI-P PY 'P phoro us acid ester H o l ll o R-NH-(CH2)JNCH2CH2CH OP--H 2H5 L 1L t-l C.., .TCH2 CH2O I H H I 0-' R stands for an alkyl radical having a chain distribu- 40 tion analogous to that of the coconut acid. 10

3-decylammonium-2-methyl-2-pr0pyl-propylphosphoro us acid ester Molecular weight: calculated: 396

found: 400 H CH3 0 Nitrogen: Calculated: 7.l 7e l A U found: 6.9 '7 C,.,H ,ll lCH,- -CH2-0- H H H7 (-l 1 i. 3-[ 2-( 2-dodecylaminoethyl )-aminoethylammonium 3-0ctadecenylammonium-2.Z-dimethyl-propyl-phosz'n'butyl'z'ethyl'propylphosphomus ester phorous acid ester H .H, o L H CH 0 IZ 25 'Z)1! !)2 2 2 I l C,,.H NCH -C|-CH -OPH H H CH3 0" Molecular weight: Calculated: 410 12 found: 45l Nitrogen: Calculated; 3,4 0; 3-( 3-coconutalkyl-N-methyl-ammo-propyl-ammonifmmd= um)-propyl-phosphorous acid ester H 0 As further examples of compounds of the formula I to l R-l\-(CH --N--CH -CH:CH-,OPH be used in accordance with the invention, there may be I l l mentioned: CH3 H M R stands for the alkyl radical having a chain distribu- -Continued tion analogous to that of the coconut fat acid. Excremem findings Judgement 13 mainly normally formed. partly liquid. 2

' mucous (green-white) 3-[3-(3-coconutalkylammopropyl)-amlnopropyl- 5 mainly liquid,watery, minimal blood =3 admixture. mucous ammonium] phosphorous acld ester liquid, mucous. distinct blood admixtures 4 H o L At the end of the test, the animals were killed with I m chloroform and the appendices were sub ected to mac- H roscopic and microscopic examination for pathological and anatomical changes.

R stands for the alkyl radical having a chain distribu- The judgen ints of the pathological changes of the tion analogous to that of the coconut acid. 5 intestinal mud sa were determined as follows:

The compounds of the formula I are used together 1 with one or several chlorinated hydrocarbons, prefera- Intestinal mucosa Judgement bly in aqueous solution, for the disinfection of rooms I d, l and objects, especially of stables and their outruns. glassycmrmm Such a disinfectant contains a mixture of 10 to 90 perfibrinous inflammations 2 cent by weight, preferably to 70 percent by weight, 20 i local hemorrhage 3 of a compound of the formula I and 90 to 10 percent by diffusepink turning into diffuse haemorrhagic weight, preferably 80 to percent by weight, of a glt 4 chlorinated hydrocarbon or a mixture of several hydrocarbons dissolved in water. Optionally, 0.1 to 10 per- 2 cent by we'ght of an emulslfierddealeulated on the com- The excretion of oocysts reveals the number of the Pound of formula may be a non s orulated ooc sts excreted in the excrement.

The disinfectant to be used is suitably diluted with p y water to a content of active substance of 0.25 to 10 percent by weight. Number of oocysts per Judgement 30 visual field l 1 2 l0 2 ll 50 3 51 200 4 EXAMPLES (Tests for activity) 20] 400 5 over 400 6 The oocyst-destroylng effect was determined according to the following method:

Oocysts of the species of Eimeria tenella were 001- The following Tables 1 and 2 Show the Synergistic leeted t the excrement of hens prevleusly e disinfection effect of the mixtures of the invention of a subleeted to the test sebstanees e the Penods of the compounds indicated in the examples with chloritlme and at the concentrations as indicated in the folnated Organic Solvents compared to the effect of aque w i The preperatlons were h h d Once ous solutions of these compounds on the one hand and l dlmethyl eormamlde and five e ,water that of chlorinated organic solvents on the other hand. eenmfuganon e the eoeyst'eentammg sedlmem Moreover, the Tables show the superior effect of the wa5husefd4f0r g erallmfeenon of ehlekens 4 e g mixtures of the invention as compared to the commere g e z app 1e were cial preparation Dekaseptol (registered trade mark) adm'mstere e treate Oocysts reportedly a mixture of chlorinated hydrocarbons, car- After termination of the test, the average body bon disulfide and a soap weght per e (absolute average j In these tests, the emulsifier used was castor oil with crease, respectively weight decrease) was ascertained. 5O ethylene Oxide in the molar ratio of 1:36

T excrement findmgs were aespeeted every day The concentrations indicated are calculated on the ing the whole test period and udged according to the Content of a compound of formula I followmg scheme: In the columns headed excrement findings, appendix findings and oocysts/unit field. each time the above- 55 mentioned judgements are indicated. Excrement findings Judgement The test results of Tables 1 and 2 have been obtained Normally fmmm Solid sporadically 1 under conditions which were not homogeneous in the pultaceous (brown) different cases and thus cannot be compared easily.

TABLE 1 Test A Preparation Period con- Excrement total number Appendix weight oocysts/ of action cen findings of surviving findings increase unit field (min) tra- +d:4.5.6 7 animals (chicken in g (chicken tion (+d=day l 4) l 4 after infection 24.7 /2 compound 1 49.5 92 o-dichlorobenzene 5 llll 4/4 llll 18.5 2l02 TABLE l-continued Test A Preparation Period con- Excrement total number Appendix weight oocysts/ of action cenfindings of surviving findings increase unit field (min) tra- +d:4.5.6.7 animals (chicken in g (chicken tion (+d=da 1 4 l 4) after infection 24.7% water 10 3 1111 4/4 1111 19.7 0021 1.2 '72 emulsifier 2O 3 1111 4/4 1111 22.8 0001 16.4 /2 compound 1 16.4 7: water 5 3 111 l 4/4 1111 20.5 0010 32.8 71 trichloro- 1 benzene 10 3 1111 4/4 1111 22.5 0000 32.8 71 o-dichlorobenzene 2O 3 111 1 4/4 1111 25.6 0000 1.6 7r emulsifier 24.7 '71 com ound 2 5 3 1111 4/4 1111 19.5 0022 49.5 72 o-dichlorobenzene l 3 1111 4/4 1111 20.5 0001 24.7 '71 water 1.2 72 emulsifier 2O 3 1111 4/4 1111 23.5 0000 DekaseptoW 6 1211 4/4 2212 13.8 2434 10 6 1111 4/4 1212 16.5 2302 6 1111 4/4 1111 18.5 2312 o-dichlorobenzene 20 12 2442 2/4 2323 8.5 4354 trichlorobcnzene I 20 12 2342 3/4 2232 9.5 2345 7( o-dichlorobcnzene 50 71 trichlorobenzene 20 24 23" 4/4 1222 12.5 2125 Infection control 20 2434 2/4 4523 7.5 3456 O-control 20 1111 4/4 1111 23.2 0000 TABLE 2 Test B Preparation Period con- Excrement total number Appendix weight oocysts/ of action cenfindings of surviving findings increase unit field (min) tra- +d:4,5.6.7 animals (chicken in g (chicken tion (+d=day 1 4) 1 4) after infection) Compound 5 20 3 2432 3/4 3434 8.2 2465 24.7 71 compound 5 49.5 '7( o-dichlorobenzene 20 3 1111 4/4 1111 18.7 2011 24.7 '71 water 1.2 '71 emulsifier compound 2 2O 3 1211 4/4 2111 14.2 2132 24.7 7: compound 2 49.5 71 o-dichlorobenzene 20 3 1 11 1 4/4 1 1 1 1 20.3 0000 24.7 7: water 1.2 "/1 emulsifier compound 3 20 3 1232 3/4 2332 2.6 6644 24.7 7: compound 3 49.5 '7! o-dichlorobenzene 20 3 1111 4/4 1111 19.2 2010 24.7 '71 water 1,2 '71 emulsifier o-dichlorbenzene 20 12 2434 3/4 2334 5.8 4543 trichlorbenzcne 20 12 3243 3/4 3334 7.9 4426 50 71 o-diclnlorobenzene 20 24 2332 4/4 2222 I 10.6 4543 50 71 trichlorbenzenc Decaseptol 20 6 1111 4/4 1111 17.0 2101 Infection control 20 2443 2/4 3454 1.8 4532 O-control 20 1 1 1 1 4/4 111 1 20.9 0000 lene chloride, chloroform, carbon tetrachloride, chlorobenzene, dichlorobenzene, trichlorobenzene, tetrachlorobenzene, ethylene chloride, trichloroethane, tetrachloroethane, tetrachloroethylene and mixtures thereof; said mixture being in the ratio of 10 to 90 percent by weight of (a) to 90 to 10 per cent by weight of What is claimed is:

1. A disinfectant composition useful against protozoan oocysts comprising a mixture of (a) a compound of the formula 2 O R'- R R b l 7 2. The disinfectant composition of claim 1 wherein H P 0 H CH. N (CH n R 1 R1 1 the ratio 15 20 to percent by weight of (a) to to 30 percent by weight of (b).

3. The disinfectant composition of claim 1 dissolved in which R is hydrogen or methyl, R R R, R and R in water in a concentration of 0.25 to 10 percent by may be the same or different and are hydrogen or alkyl weight.

of 1 to 4 carbon atoms, R is alkyl of 8 to 18 carbon 65 4. The disinfectant composition of claim 1 wherein atoms or alkenyl of 8 to 18 carbon atoms, 11 is 2 or 3 compound (a) is a 3-(3-coconut alkyl aminopropyland m is zero or 1 to 4; and (b) a chlorinated organic ammonium)-2,Z-dimethylpropyl-phosphorus acid essolvent selected from the group consisting of methyter.

8. The disinfectant composition of claim 1 wherein compound (a) is 3-octadecenylammonuim-2,2-dimethylpropyl-phosphorus acid ester.

9. A method of destroying protozoan oocysts which comprises applying an effective amount of the composition of claim 1 diluted with water to a concentration of 0.25 to 10 percent by weight to the loci of said 00- cysts 

1. A DISINFECTANT COMPOSITION USEFUL AGAINST PROTOZOAN OOCYSTS COMPRISING A MIXTURE OF (A) A COMPOUND OF THE FORMULA
 2. The disinfectant composition of claim 1 wherein the ratio is 20 to 70 percent by weight of (a) to 80 to 30 percent by weight of (b).
 3. The disinfectant composition of claim 1 dissolved in water in a concentration of 0.25 to 10 percent by weight.
 4. The disinfectant composition of claim 1 wherein compound (a) is a 3-(3-coconut alkyl aminopropyl-ammonium)-2,2-dimethylpropyl-phosphorus acid ester.
 5. The disinfectant composition of claim 1 wherein compound (a) is a 3-coconut alkyl ammonium-2, 2-dimethylpropyl-phosphorus acid ester.
 6. The disinfectant composition of claim 1 wherein compound (a) is 3-(2-(2-dodecylaminoethyl)-aminoethyl-ammonium)-2,2-dimethyl-propyl -phosphorus acid ester.
 7. The disinfectant composition of claim 1 wherein compound (a) is a 3-(coconut-alkylaminopropyl-ammonium)-propyl-phosphorus acid ester.
 8. The disinfectant composition of claim 1 wherein compound (a) is 3-octadecenylammonuim-2,2-dimethylpropyl-phosphorus acid ester.
 9. A method of destroying protozoan oocysts which comprises applying an effective amount of the composition of claim 1 diluted with water to a concentration of 0.25 to 10 percent by weight to the loci of said oocysts. 